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PubMed2005

Evidence of a large-scale functional organization of mammalian chromosomes.

Evidence from inbred strains of mice indicates that a quarter or more of the mammalian genome consists of chromosome regions containing clusters of functionally related genes. The intense selection pressures during inbreeding favor the coinheritance of optimal sets of alleles among these genetically linked, functionally related genes, resulting in extensive domains of linkage disequilibrium (LD) among a set of 60 genetically diverse inbred strains. Recombination that disrupts the preferred combinations of alleles reduces the ability of offspring to survive further inbreeding. LD is also seen between markers on separate chromosomes, forming networks with scale-free architecture. Combining LD data with pathway and genome annotation databases, we have been able to identify the biological functions underlying several domains and networks. Given the strong conservation of gene order among mammals, the domains and networks we find in mice probably characterize all mammals, including humans.

Animals↗
PubMed2004

Characterization of conditionally expressed mutants affecting age-specific survival in inbred lines of Drosophila melanogaster: lethal conditions and temperature-sensitive periods.

The specific genetic basis of inbreeding depression is poorly understood. To address this question, two conditionally expressed lethal effects that were found to cause line-specific life span reductions in two separate inbred lines of Drosophila melanogaster were characterized phenotypically and genetically in terms of whether the accelerated mortality effects are dominant or recessive. The mortality effect in one line (I4) is potentially a temperature-sensitive semilethal that expresses in adult males only and is partially dominant. The other line (I10) responds as one would expect for a recessive lethal. It requires a cold shock for expression and is cold sensitive. Flies exhibiting this lethal condition responded as pupae and freshly eclosed imagoes. The effect is recessive in both males and females. The expression of the lethal effects in both lines is highly dependent upon environmental conditions. These results will serve as a basis for more detailed and mechanistic genetic research on inbreeding depression and are relevant to sex- and environment-specific effects on life span observed in quantitative trait loci studies using inbred lines.

Animals↗
PubMed2004

The effective size of mixed sexually and asexually reproducing populations.

Using the transition matrix of inbreeding and coancestry coefficients, the inbreeding (N(eI)), variance (N(eV)), and asymptotic (N(e lambda)) effective sizes of mixed sexual and asexual populations are formulated in terms of asexuality rate (delta), variance of asexual (C) and sexual (K) reproductive contributions of individuals, correlation between asexual and sexual contributions (rho(ck)), selfing rate (beta), and census population size (N). The trajectory of N(eI) toward N(e lambda) changes crucially depending on delta, N, and beta, whereas that of N(eV) is rather consistent. With increasing asexuality, N(e lambda) either increases or decreases depending on C, K, and rho(ck). The parameter space in which a partially asexual population has a larger N(e lambda) than a fully sexual population is delineated. This structure is destroyed when N(1 - delta) < 1 or delta > 1 - 1/N. With such a high asexuality, tremendously many generations are required for the asymptotic size N(e lambda) to be established, and N(e lambda) is extremely large with any value of C, K, and rho(ck) because the population is dominated eventually by individuals of the same genotype and the allelic diversity within the individuals decays quite slowly. In reality, the asymptotic state would occur only occasionally, and instantaneous rather than asymptotic effective sizes should be practical when predicting evolutionary dynamics of highly asexual populations.

Alleles↗
PubMed2002

Establishment of inbred strains of chicken and Japanese quail and their potential as animal models.

We started establishing inbred strains of chicken and Japanese quail in 1970. In class Aves, full sib mating is highly difficult due to inbreeding depression. In the chicken, we attempted to establish some inbred strains in three breeds, Black Minorca, White Leghorn and Fayoumi by fixing all the characters that differentiate individuals homozygously. In this paper, we describe some marker genes and characters fixed in the inbred strains of chicken and Japanese quail as well as a calculation of a putative coefficient of inbreeding in 8 chicken inbred strains using band sharing values detected by AFLP analysis. We established generalized glycogenosis type II quail, myotonic dystrophy quail, neurofilament deficient quail, visually impaired chicken, double oviduct chicken with partial kidney deficiency, chicken showing spontaneous lymphocytic thyroiditis with feathered amelanosis, and chicken with a hereditary nervous disorder. The processes of establishment and characteristics of these animal models are described with some interesting information obtained from these animal models. In generalized glycogenosis type II quail, the results of enzyme replacement therapy and gene therapy are described.

Animals↗
PubMed1990

Estimation of additive genetic variance when base populations are selected.

A population of size 40 was simulated 1,000 times for 10 generations. Five out of twenty males were selected each generation, and each male was mated to four females to have two progeny. The additive genetic variance (sigma 2a) before selection was 10, and the initial heritability was .5. Due to covariances among animals, inbreeding and gametic disequilibrium, the genetic variance was reduced to 6.72 after 10 generations of selection. Reduction of variance was lower in another population simulated with size 400 and 10% of the males selected. Restricted Maximum Likelihood was used to estimate sigma 2a using an animal model. The estimate of sigma 2a was empirically unbiased when all data and all relationships were used. Omitting data from selected ancestors caused biased estimates of sigma 2a due to not accounting for all gametic disequilibrium. Including additional relationships between assumed base animals adjusted for inbreeding and for covariances. Bias from gametic disequilibrium decreased slightly with the use of more relationship information, and it was smaller in the small population and(or) when selection had been practiced for just a few generations.

Animals↗
PubMed1992

Selection for postweaning growth in inbred Hereford cattle: the Fort Keogh, Montana line 1 example.

Demographic characteristics and genetic trends in birth weight and pre- and postweaning ADG were examined in a population of Hereford cattle (Line 1). Line 1 was founded largely from two paternal half-sib sires and has been selected for postweaning growth. There were pedigree records on 951 members of the base population that predated 1935, when data collection began. Numbers of records analyzed using mixed-model methodology were 4,716 birth weight, 4,427 preweaning ADG, and 3,579 postweaning ADG. Birth weight and preweaning ADG were considered to have direct and maternal genetic components. Inbreeding accumulated rapidly from 1935 to 1960 and more slowly (.22%/yr) thereafter. Any reduction in additive genetic variance due to inbreeding and selection may have been offset by a concurrent reduction in generation interval that was observed as time progressed. Expected selection differential for 365-d weight, averaged over sexes, was 31.2 kg per generation. For birth weight, annual genetic trends in direct and maternal effects were 42 +/- 3 g and 15 +/- 3 g, respectively. Annual direct and maternal genetic trends for preweaning ADG were .70 +/- .06 g/d and .63 +/- .06 g/d, respectively. Direct response in postweaning ADG was linear and equal to 5.3 +/- .6 g.d-1.yr-1. As a result, estimated breeding values of birth weight, 200-d weight, and 365-d weight increased by 3.2 kg, 14.5 kg, and 62.4 kg, respectively, from 1935 to 1989. Selection within Line 1 was effective in increasing genetic potential for growth over 13 generations. No selection plateau was observed in any of the traits examined.

Age Factors↗
PubMed1998

Estimation of the dominance variance for postweaning gain in the U.S. Limousin population.

The objective of this study was to estimate the dominance variance for postweaning gain in Limousin cattle. Data included 215,326 records of postweaning gain from 205 to 365 d, provided by the North American Limousin Foundation. Parental dominance subclasses were formed and related using the method of Hoeschele and VanRaden. Variance components were estimated using Method R based on six samples of 50%. Fixed effects in the model included contemporary group and covariates for inbreeding and breed composition (percentage Limousin). Heterozygosity was negatively correlated with breed composition (< -.99) and was therefore not included in the model. Two types of contemporary groups used as original groups from the National Cattle Evaluation were partially based on breed composition. Original contemporary groups that were too homogeneous for breed composition were replaced by herd-year-sex classes. Two models were used with the two data sets. Model 1 contained the fixed effects described above and an additive genetic effect. Model 2 included a dominance effect in addition to the effects contained in Model 1. In total, four combinations of contemporary group x model were used. Dominance variance was computed as being four times the estimated parental subclass variance. Estimates for inbreeding depression and breed composition (percentage Limousin) were all small and not greatly affected by inclusion of dominance effects or changes in contemporary groups. Estimates of the additive variance (expressed as percentage of the phenotypic variance) were only slightly affected, with values between 20 and 21%. Dominance estimates were highly affected when passing from original (10%) and to alternative contemporary groups (18%). Such large values may indicate that dominance is important for postweaning gain. Results showed the advantage of an individual dominance approach based on sire-dam combinations; therefore, expected gains through the use of specific combination ability as a part of the mating selection criteria for growth might be high.

Animals↗
PubMed1983

Pedigree analysis of four decades of Quarter Horse breeding.

Pedigrees of randomly selected Quarter Horses born in each of the years 1946, 1956, 1966 and 1976 and of winning halter, cutting and race horses born in the same years were evaluated and compared. Average inbreeding and inter se relationship levels and relationships of influential ancestors to the sample were calculated for each sample. The amount of Thoroughbred influence and the average generation interval were also determined for each random sample. The levels of inbreeding found in the random samples were low, ranging from 1.3% in 1956 to 2.6% in 1966; however, these levels were higher than would be expected if mating were random. Show and race winners born in 1976 appeared to be less inbred than random horses of the breed. The estimated average inter se relationship within the random samples increased from 0% in 1946 to 3% in 1966, decreasing again to 0% in 1976. Horses in the elite samples appeared to be more closely related to each other than those in the random samples. Fifteen ancestors of horses in the random samples were identified as influential to the Quarter Horse breed. Many of these same ancestors were influential in the halter and cutting samples, but only one was influential in the race samples. The percentage of pedigree lines in the random samples that contained a Thoroughbred ancestor were as follows; 1946, 27.5%; 1956, 19.2%; 1966, 23.2% and 1976, 31.4%. The average generation interval fluctuated from approximately 8 yr to approximately 10 yr for the random samples.

Animals↗
PubMed1983

Reciprocal recurrent selection for 21-day litter weight of crossbred gilts. II. Reproductive performance of purebred females producing purebred and two-way cross litters and performance of purebred and crossbred pigs.

This paper reports estimates of correlated genetic change in reproductive performance of purebred gilts producing two-way cross litters and purebred sows producing purebred litters as well as postweaning performance of two-way cross and purebred pigs produced during reciprocal recurrent selection (RRS) between Line 8 (Duroc) and Line 9 (Beltsville No. 1) for 21-d litter weight production of crossbred gilts. A randomly mated control line developed from a crossbred foundation was maintained to monitor environmental change. Data were adjusted for age of dam, inbreeding of dam, inbreeding of litter (or pig) and linear and quadratic effects of day born within season. The traits evaluated were: litter size, litter weight and average pig weight/litter at birth and weaning (42 d); postweaning average daily gain; age at 90.7 kg and backfat thickness at 90.7 kg. Two data sets were analyzed; the first set included seven seasons of data with purebred gilts producing two-way cross litters, and the second set included seven seasons of data with purebred sows producing purebred litters. No estimates of environmental trend were significant in either set of data. In the first data set, only the estimate of genetic change in backfat thickness of two-way cross pigs was significant and it was in the desired direction. All other estimates were small and did not approach significance. In the second data set, estimates of genetic trend were greater in Line 9 than in Line 8.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Estimation of genetic parameters among breeding soundness examination components and growth traits in yearling bulls.

Data on breeding soundness examinations (BSE) and performance traits were obtained on 549 yearling beef bulls at the San Juan Basin Research Center, Hesperus, Co from 1976 to 1984. Genetic parameters estimated for components of BSE included percent motility (PMOT), percent primary abnormalities (PPRIM), percent secondary abnormalities (PSEC), percent normal sperm (PNOR), scrotal circumference (SC) and BSE score (BSESC). Performance traits included birth weight, weaning weight, yearling weight and average daily gain. The least squares model included birth year, age of dam and breed as fixed effects, sire/breed as a random variable, and age and percent inbreeding as covariates. Paternal half-sib estimates of heritability were PMOT, .08 +/- .07; PPRIM, .31 +/- .09; PSEC, .02 +/- .05; PNOR, .07 +/- .06; BSESC, .10 +/- .06 and SC, .40 +/- .09. Phenotypic correlations among BSE components and growth traits were generally favorable. Genetic correlations involving percent secondary abnormalities were highly variable with large standard errors. Seminal traits improved as age increased and became poorer as inbreeding increased.

Age Factors↗
PubMed1989

Deficiency of the corpus callosum: incomplete penetrance and substrain differentiation in BALB/c mice.

In a foundation population of BALB/c mice used to establish a colony at Waterloo in 1977, about 11% of adults showed either total absence or gross deficiency of the corpus callosum. Comparisons between parents and offspring, between progenies of different males, and between 13 separate lines established by full-sib inbreeding showed that variation in the adult corpus callosum reflected a genuine incomplete penetrance in a genetically uniform population. However, after seven generations of inbreeding, a spontaneous change occurred in one line (BALB/cWah 1), resulting in more than 50% of adults with deficient corpus callosum, among which about 20% have complete absence of callosal axons traversing the hemispheres.

Agenesis of Corpus Callosum↗
PubMed2006

Major advances in genetic evaluation techniques.

The past quarter-century in genetic evaluation of dairy cattle has been marked by evolution in methodology and computer capacity, expansion in the array of evaluated traits, and globalization. Animal models replaced sire and sire-maternal grandsire models and, more recently, application of Bayesian theory has become standard. Individual test-day observations have been used more effectively in estimation of lactation yield or directly as input to evaluation models. Computer speed and storage are less limiting in choosing procedures. The increased capabilities have supported evaluation of additional traits that affect the net profitability of dairy cows. The importance of traits other than yield has increased, in a few cases due to an antagonistic relationship with yield. National evaluations combined internationally provide evaluations for bulls from all participating countries on each of the national scales, facilitating choices from among many more bulls. Selection within countries has increased inbreeding and the use of similar genetics across countries reduces the previously available outcross population. Concern about inbreeding has prompted changes in evaluation methodology and mating practices, and has promoted interest in crossbreeding. In just the past decade, distribution of genetic evaluations has gone from mailed paper or computer tapes for a limited audience to publicly accessible, request-driven distribution via the Internet. Among the distributed information is a choice of economic indices that combine an increasing array of traits into numbers reflecting breeding goals under different milk-pricing conditions. Considerable progress in genomics and the mapping of the bovine genome have identified markers for some deleterious recessive genes, but broader benefits of marker-assisted selection are still in the future. A possible exception is the proprietary use of DNA testing by semen producers to select among potential progeny test bulls. The collection and analysis of industry-wide data to evaluate genetic merit will continue to be the most important tool for genetic progress into the foreseeable future.

Animals↗
PubMed1995

Visualization of inheritance patterns from graphic representation of additive and dominance relationships between animals.

Evaluation of pedigrees of normal and affected individuals help to suggest possible patterns of inheritance. Because large numbers of individuals are involved in studies of genetic disease, classic two-dimensional family tree charts are difficult to draw. Instead, DFA plots of graduated circles, weighted by dominance relationships, inbreeding, and additive relationships between individuals can be plotted above, on, and below the diagonal. Base animals without phenotypic measurements contribute information for computation of approximate dominance relationship, inbreeding, and additive relationships, but are not explicitly in the graph. Plotting only a set of randomly selected animals for each combination of phenotypes improves the visualization effect, especially when pedigrees are large or when computer resources are limited. For deficiency of uridine monophosphate synthase and interdigital hyperplasia, DFA plots showed higher densities of additive and dominance relationships among affected animals. However, DFA plots did not show clear patterns of inheritance for heel erosion, laminitis, or sole ulcers because environmental effects were important for those traits. Grouped graduated circles also improved visualization. The function of DFA plots is comparable with statistical scatter plots that display data to help examine statistical approaches. The DFA plots serve as a first approach to evaluate genetic hypotheses before a more complex model is fit.

Animals↗
PubMed1998

Effect of full sibs on additive breeding values under the dominance model for stature in United States Holsteins.

Differences in breeding values between dominance and additive models were examined theoretically and with field data. Data included 5.2 million records on stature from 3.0 million US Holsteins. The largest full-sib family had 29 animals, and 7% of all animals had at least one full sib. The dominance model, which accounted for dominance covariances, included the following effects: management, age, stage of lactation, permanent environment, animal additive, and parental dominance (one-quarter of dominance variance) as well as a regression coefficient for inbreeding percentage. Two reduced models were also assumed; in the first, the parental dominance effect was removed, and, in the second, the inbreeding regression coefficient was also removed. The correlations between breeding values in the three models were > 0.999, but breeding values of some animals from full-sib families changed > 5 standard deviations of parental dominance. The largest changes were observed for parents with large numbers of full-sib progeny, with limited information from parents, and without individual performance records. On average, the differences were up to four times larger for cows than for bulls and up to five times larger for dams than for sires. The greatest differences in breeding values between the dominance and the additive models were observed for dams with full-sib progeny, female full sibs, and low reliability bulls with full sibs in the extended family. Animals with large amounts of additive information as progeny-tested bulls were influenced little by the inclusion of dominance. Animals with a large proportion of information coming from animals with dominance relationships, such as cows originating via embryo transfer changed the most.

Animals↗
PubMed1991

Heterozygosity at protein loci in inbred and outbred lines of chickens.

Levels of heterozygosity at six polymorphic protein marker loci were determined by electrophoresis in 24 lines of poultry, encompassing 17 White Leghorn inbred lines (WLI) (with inbreeding coefficients, F, ranging from .946 to .988), five Australorp inbred lines (AusI) (with F values ranging from .924 to .961), and two randombred lines (one White Leghorn and one Australorp). Fixation was observed at one locus in WLI lines, and at two loci in the AusI lines. Segregation at the other loci was observed in the inbred lines of the two breeds. Observed heterozygosity in the inbred lines markedly exceeded the expectations under inbreeding theory. In White Leghorns, reproductive fitnesses for heterozygotes were superior to homozygotes in the inbred lines, but not in the control. Consequently, natural selection operating through associative overdominance appears to be responsible for the higher than expected heterozygosities in the inbred lines.

Animals↗
PubMed1995

Comparison of index selection and best linear unbiased prediction for simulated layer poultry data.

The advantage of using best linear unbiased prediction (BLUP) of breeding value over different selection indexes was examined for a sex-limited trait in a simulated layer poultry population. The base breeding population consisted of 30 males and 300 females that were unrelated to each other. Heritability for different analyses was assumed to be either .1, .2, or .5. Each generation was reproduced from two hatches each year, with a hatch variance of 3.165% of the phenotypic variance, except for one simulation, in which it was assumed to be 40% to test the effect of a large fixed effect. Parents were selected on 1) BLUP of breeding value, 2) optimum selection index (individual, full-, and half-sibs), 3) classical selection index (as for optimum, but index weight constant across generations), 4) reduced selection index (individual and full-sibs only), or 5) combination of classical and BLUP. The relative selection response with the selection indices compared to the BLUP estimates (except for the reduced selection index) were from 94.5 to 99.4% of BLUP. Inbreeding was higher in the BLUP selected populations, which could offset any advantage of BLUP if the populations were structured so that inbreeding could rise too rapidly.

Animals↗
PubMed1996

Skin allograft survival in chicken strains with spontaneous autoimmune diseases.

Skin grafts were performed to prove the level of genetic diversity in chicken populations of the Obese strain (OS), which develops a spontaneous Hashimoto's-like thyroiditis, and University of California at Davis (UCD) Line-200 chickens, which are hereditarily afflicted with progressive systemic sclerosis (scleroderma). As controls, Cornell C-strain (CS) and inbred, normal White Leghorn CB chickens were included in the genetic monitoring program. At the commencement of this study in 1988, median allograft rejections were observed after 9 to 12 d (range 8 to 14 d) in OS and CS chickens that derived from large flocks at Cornell University, whereas OS sublines of the smaller, more closely-bred colonies at the University of Innsbruck, Austria, showed median allograft rejection after 19 d (range 12 to 35 d). From 1988 to 1993, allograft survival was only slightly prolonged in the OS sublines. However, the results of the skin allotransplantations in inbred UCD-200 chickens revealed two subpopulations in this line. In one subgroup the median of allograft rejection was calculated with 13 d (range 6 to 37 d) in 1989, 30 d (10 to 37 d) in 1990, 21 d (8 to 90 d) in 1991, and 16 d (7 to 26 d) in 1993. In the other subgroup allografts were accepted at rates similar to autografts. In addition, the inbreeding coefficient was calculated for eight male and eight female OSB5B5Cornell (C) and OSB5B5Innsbruck (INN) chickens, respectively, hatched in 1993. On the basis of mating records, the minimal estimate of the inbreeding coefficient was calculated to be 0.0679 in the OSB5B5C and 0.1035 in the OSB5B5INN population. The results demonstrated a higher degree of consanguinity in the smaller population of OSB5B5INN chickens compared to OSB5B5C birds. The later are maintained in larger numbers, therefore, the frequency of matings between related individuals should be lower.

Animals↗
PubMed2002

Cryptorchidism in Florida panthers: prevalence, features, and influence of genetic restoration.

The overall prevalence of cryptorchidism in Florida panthers (Puma concolor coryi) from 1972-2001 was 49% (24/49), with a significant increase over time. The earliest age at which descent of both testicles was known to occur was 2 mo and the latest was 10-13 mo. Delayed testicular descent was documented in 23% (8/35) of juveniles examined. Most retained testicles were in the inguinal canal. There was no apparent difference in reproductive success between cryptorchid and normal panthers, although no bilaterally cryptorchid panthers were known to have sired litters. Cryptorchidism was thought to be a manifestation of inbreeding and was one of several factors that led to the development of a genetic restoration plan whereby eight female puma from Texas were released into the panther population in 1995. None of the progeny resulting from genetic restoration efforts has been cryptorchid. This report provides evidence that cryptorchidism in panthers is genetically rather than environmentally based, and demonstrates the utility of genetic restoration for eliminating certain deleterious traits that result from inbreeding.

Animals↗